All roads lead to Rome, but someone are safer

Since the first in-human implantation, trans-catheter aortic valve replacement (TAVR) has shown an exciting development in both technical and technological terms, becoming the standard of care for many patients, even not only inoperable ones. Although trans-femoral (TF) access has the scepter of first-line route for TAVR, in some cases, this access is not feasible, so several alternative routes were introduces over time. The network meta-analysis by Hameed et al has the great merit to provide a comprehensive picture. Hence, through either direct and indirect comparison, the authors confirmed as TF is the gold standard as access, followed by trans-carotid and trans-subclavian. Conversely, trans-thoracic (trans apical and trans-aortic) routes are the least safe and should be reserved only to sporadic cases.

Histological Analysis of Cartilage Defects Repaired with an Autologous Human Stem Cell Construct 48 Weeks Postimplantation Reveals Structural Details Not Detected by T2-Mapping MRI

Objective The aim of this study was to elucidate the efficacy of T2-mapping MRI and correlation with histology for the evaluation of tissue repair quality following the first-in-human implantation of an autologous tissue engineered construct. Design We directly compared the results of T2-mapping MRI of cartilage repair tissue with the histology of a biopsy specimen from the corresponding area at 48 weeks postoperatively in 5 patients who underwent the implantation of a scaffold-free tissue-engineered construct generated from autologous synovial mesenchymal stem cells to repair an isolated cartilage lesion. T2 values and histological scores were compared at each of 2 layers of equally divided halves of the repair tissue (upper and lower zones). Results Histology showed that the repair tissue in the upper zone was dominated by fibrous tissue and the ratio of hyaline-like matrix increased with the depth of the repair tissue. There were significant differences between upper and lower zones in histological scores. Conversely, there were no detectable statistically significant differences in T2 value detected among zones of the repair tissue, but zonal differences were detected in corresponding healthy cartilage. Accordingly, there were no correlations detected between histological scores and T2 values for each repair cartilage zone. Conclusion Discrepancies in the findings between T2 mapping and histology suggest that T2 mapping was limited in ability to detect details in the architecture and composition of the repair cartilage.

Trophectoderm differentiation to invasive syncytiotrophoblast is induced by endometrial epithelial cells during human embryo implantation

At implantation, trophoblast derived from the trophectoderm of the blastocyst-stage embryo invades the endometrium to establish pregnancy. To understand how embryos breach the endometrial epithelium, we modelled human implantation using blastocysts or trophoblast stem cell spheroids cultured with endometrial epithelial cells (EEC). Blastocyst invasion of the EEC layer was initiated by multinuclear syncytiotrophoblast. Spheroids also invaded the epithelium with syncytiotrophoblast, and EEC induced upregulation of syncytiotrophoblast markers. Modelling implantation in silico using blastocyst and EEC transcriptomes revealed gene networks that exhibited greater connectivity and organisation in trophectoderm of the polar region of the embryonic axis. However, gene ontologies and machine learning suggested that EEC drives syncytiotrophoblast differentiation in polar and mural trophectoderm. This is the first evidence for endometrial epithelium-induced trophectoderm differentiation to invasive syncytiotrophoblast as the cellular mechanism of embryonic breaching of the endometrium in humans, with implications for reproductive medicine and our understanding of human embryonic development.

Identifying biomarkers for predicting successful embryo implantation: applying single to multi-OMICs to improve reproductive outcomes

BACKGROUND Successful embryo implantation is a complex process that requires the coordination of a series of events, involving both the embryo and the maternal endometrium. Key to this process is the intricate cascade of molecular mechanisms regulated by endocrine, paracrine and autocrine modulators of embryonic and maternal origin. Despite significant progress in ART, implantation failure still affects numerous infertile couples worldwide and fewer than 10% of embryos successfully implant. Improved selection of both the viable embryos and the optimal endometrial phenotype for transfer remains crucial to enhancing implantation chances. However, both classical morphological embryo selection and new strategies incorporated into clinical practice, such as embryonic genetic analysis, morphokinetics or ultrasound endometrial dating, remain insufficient to predict successful implantation. Additionally, no techniques are widely applied to analyse molecular signals involved in the embryo–uterine interaction. More reliable biological markers to predict embryo and uterine reproductive competence are needed to improve pregnancy outcomes. Recent years have seen a trend towards ‘omics’ methods, which enable the assessment of complete endometrial and embryonic molecular profiles during implantation. Omics have advanced our knowledge of the implantation process, identifying potential but rarely implemented biomarkers of successful implantation. OBJECTIVE AND RATIONALE Differences between the findings of published omics studies, and perhaps because embryonic and endometrial molecular signatures were often not investigated jointly, have prevented firm conclusions being reached. A timely review summarizing omics studies on the molecular determinants of human implantation in both the embryo and the endometrium will help facilitate integrative and reliable omics approaches to enhance ART outcomes. SEARCH METHODS In order to provide a comprehensive review of the literature published up to September 2019, Medline databases were searched using keywords pertaining to omics, including ‘transcriptome’, ‘proteome’, ‘secretome’, ‘metabolome’ and ‘expression profiles’, combined with terms related to implantation, such as ‘endometrial receptivity’, ‘embryo viability’ and ‘embryo implantation’. No language restrictions were imposed. References from articles were also used for additional literature. OUTCOMES Here we provide a complete summary of the major achievements in human implantation research supplied by omics approaches, highlighting their potential to improve reproductive outcomes while fully elucidating the implantation mechanism. The review highlights the existence of discrepancies among the postulated biomarkers from studies on embryo viability or endometrial receptivity, even using the same omic analysis. WIDER IMPLICATIONS Despite the huge amount of biomarker information provided by omics, we still do not have enough evidence to link data from all omics with an implantation outcome. However, in the foreseeable future, application of minimally or non-invasive omics tools, together with a more integrative interpretation of uniformly collected data, will help to overcome the difficulties for clinical implementation of omics tools. Omics assays of the embryo and endometrium are being proposed or already being used as diagnostic tools for personalised single-embryo transfer in the most favourable endometrial environment, avoiding the risk of multiple pregnancies and ensuring better pregnancy rates.